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. 1986 Dec;83(23):8929–8933. doi: 10.1073/pnas.83.23.8929

Interferon-stimulated transcription: isolation of an inducible gene and identification of its regulatory region.

D Levy, A Larner, A Chaudhuri, L E Babiss, J E Darnell Jr
PMCID: PMC387047  PMID: 3466167

Abstract

A human gene (termed ISG-54K) that is induced from near undetectable levels to high transcriptional activity by alpha- and beta-interferons has been cloned. The genomic structure and nucleotide sequence of the coding region were determined and the RNA initiation site was identified. The 5' portion of the gene was fused with a heterologous gene lacking an active promoter in recombinant plasmid and adenoviral vectors. These fusion genes were used to assess the activity of the ISG-54K promoter in response to interferon. RNA was formed in HeLa cells from recombinant plasmids only in response to interferon. Furthermore, in human diploid fibroblasts, infection with the recombinant adenovirus vector resulted in a 50-fold increase in specific RNA in response to interferon, followed by a subsequent decrease, imitating the natural regulated transcriptional cycle of the endogenous gene.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Benech P., Merlin G., Revel M., Chebath J. 3' end structure of the human (2'-5') oligo A synthetase gene: prediction of two distinct proteins with cell type-specific expression. Nucleic Acids Res. 1985 Feb 25;13(4):1267–1281. doi: 10.1093/nar/13.4.1267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berridge M. J., Irvine R. F. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984 Nov 22;312(5992):315–321. doi: 10.1038/312315a0. [DOI] [PubMed] [Google Scholar]
  3. Blomstrom D. C., Fahey D., Kutny R., Korant B. D., Knight E., Jr Molecular characterization of the interferon-induced 15-kDa protein. Molecular cloning and nucleotide and amino acid sequence. J Biol Chem. 1986 Jul 5;261(19):8811–8816. [PubMed] [Google Scholar]
  4. Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
  5. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Friedman R. L., Manly S. P., McMahon M., Kerr I. M., Stark G. R. Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells. Cell. 1984 Oct;38(3):745–755. doi: 10.1016/0092-8674(84)90270-8. [DOI] [PubMed] [Google Scholar]
  7. Gilman A. G. G proteins and dual control of adenylate cyclase. Cell. 1984 Mar;36(3):577–579. doi: 10.1016/0092-8674(84)90336-2. [DOI] [PubMed] [Google Scholar]
  8. Greenberg M. E., Ziff E. B. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature. 1984 Oct 4;311(5985):433–438. doi: 10.1038/311433a0. [DOI] [PubMed] [Google Scholar]
  9. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  10. Kelly J. M., Gilbert C. S., Stark G. R., Kerr I. M. Differential regulation of interferon-induced mRNAs and c-myc mRNA by alpha- and gamma-interferons. Eur J Biochem. 1985 Dec 2;153(2):367–371. doi: 10.1111/j.1432-1033.1985.tb09312.x. [DOI] [PubMed] [Google Scholar]
  11. Kelly J. M., Porter A. C., Chernajovsky Y., Gilbert C. S., Stark G. R., Kerr I. M. Characterization of a human gene inducible by alpha- and beta-interferons and its expression in mouse cells. EMBO J. 1986 Jul;5(7):1601–1606. doi: 10.1002/j.1460-2075.1986.tb04402.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Knight E., Jr, Korant B. D. Fibroblast interferon induces synthesis of four proteins in human fibroblast cells. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1824–1827. doi: 10.1073/pnas.76.4.1824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Larner A. C., Chaudhuri A., Darnell J. E., Jr Transcriptional induction by interferon. New protein(s) determine the extent and length of the induction. J Biol Chem. 1986 Jan 5;261(1):453–459. [PubMed] [Google Scholar]
  14. Larner A. C., Jonak G., Cheng Y. S., Korant B., Knight E., Darnell J. E., Jr Transcriptional induction of two genes in human cells by beta interferon. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6733–6737. doi: 10.1073/pnas.81.21.6733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lengyel P. Biochemistry of interferons and their actions. Annu Rev Biochem. 1982;51:251–282. doi: 10.1146/annurev.bi.51.070182.001343. [DOI] [PubMed] [Google Scholar]
  16. Leonard W. J., Krönke M., Peffer N. J., Depper J. M., Greene W. C. Interleukin 2 receptor gene expression in normal human T lymphocytes. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6281–6285. doi: 10.1073/pnas.82.18.6281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lopata M. A., Cleveland D. W., Sollner-Webb B. High level transient expression of a chloramphenicol acetyl transferase gene by DEAE-dextran mediated DNA transfection coupled with a dimethyl sulfoxide or glycerol shock treatment. Nucleic Acids Res. 1984 Jul 25;12(14):5707–5717. doi: 10.1093/nar/12.14.5707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mount S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. doi: 10.1093/nar/10.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Murdoch G. H., Potter E., Nicolaisen A. K., Evans R. M., Rosenfeld M. G. Epidermal growth factor rapidly stimulates prolactin gene transcription. Nature. 1982 Nov 11;300(5888):192–194. doi: 10.1038/300192a0. [DOI] [PubMed] [Google Scholar]
  21. Proudfoot N. J., Brownlee G. G. 3' non-coding region sequences in eukaryotic messenger RNA. Nature. 1976 Sep 16;263(5574):211–214. doi: 10.1038/263211a0. [DOI] [PubMed] [Google Scholar]
  22. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Staeheli P., Haller O., Boll W., Lindenmann J., Weissmann C. Mx protein: constitutive expression in 3T3 cells transformed with cloned Mx cDNA confers selective resistance to influenza virus. Cell. 1986 Jan 17;44(1):147–158. doi: 10.1016/0092-8674(86)90493-9. [DOI] [PubMed] [Google Scholar]
  24. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Yoshie O., Schmidt H., Lengyel P., Reddy E. S., Morgan W. R., Weissman S. M. Transcripts of human HLA gene fragments lacking the 5'-terminal region in transfected mouse cells. Proc Natl Acad Sci U S A. 1984 Feb;81(3):649–653. doi: 10.1073/pnas.81.3.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Zullo J. N., Cochran B. H., Huang A. S., Stiles C. D. Platelet-derived growth factor and double-stranded ribonucleic acids stimulate expression of the same genes in 3T3 cells. Cell. 1985 Dec;43(3 Pt 2):793–800. doi: 10.1016/0092-8674(85)90252-1. [DOI] [PubMed] [Google Scholar]

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